eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Genetics

Prader-Willi Syndrome

Ann Scheimann, MD, MBA, Associate Professor, Department of Pediatrics, Section of Nutrition and Gastroenterology, Baylor College of Medicine and Johns Hopkins Medical Institution

Updated: Jul 27, 2009

Introduction

Background

Prader-Willi syndrome (PWS) is a disorder caused by a deletion or disruption of genes in the proximal arm of chromosome 15 or by maternal disomy in the proximal arm of chromosome 15. Commonly associated characteristics of this disorder include diminished fetal activity, obesity, hypotonia, mental retardation, short stature, hypogonadotropic hypogonadism, strabismus, and small hands and feet.

In 1887, Langdon-Down described the first patient with Prader-Willi syndrome as an adolescent girl with mental impairment, short stature, hypogonadism, and obesity and attributed these symptoms to polysarcia.¹ In 1956, Prader et al reported a series of patients with similar phenotypes.² In 1981, Ledbetter et al identified microdeletions within chromosome 15 and determined it to be the site for Prader-Willi syndrome.^3,4

Pathophysiology

Prader-Willi syndrome is the first human disorder attributed to genomic imprinting. In such disorders, genes are expressed differentially based on the parent of origin. An imprinting center has been identified within 15q11-13; gene expression may be regulated by DNA methylation at cytosine bases.⁵ Prader-Willi syndrome results from the loss of imprinted genomic material within the paternal 15q11.2-13 locus. The loss of maternal genomic material at the 15q11.2-13 locus results in Angelman syndrome.⁶

Most cases of Prader-Willi syndrome that involve deletions, unbalanced translocations, and uniparental (maternal) disomy are sporadic. Monozygotic twins are concordantly affected. Approximately 70% of Prader-Willi syndrome cases arise from deletion of band 15q11-13 on chromosome 15. Maternal uniparental disomy caused by chromosomal nondisjunction accounts for 28% of Prader-Willi syndrome cases.⁷ Less than 1% of patients have mutations isolated to the imprinting center, which carries a risk of recurrence.⁸ Buiting et al have suggested that deletions solely localized to the imprinting center may be due to a failure to erase the maternal imprint during spermatogenesis.⁹

Several genes have been mapped to the 15q11.2-13 region, including the SNRPN gene, P gene (type II oculocutaneous albinism),¹⁰ UBE3A gene (encodes a ubiquitin-protein ligase involved in intracellular protein turnover), and necdin gene (codes for a nuclear protein expressed exclusively in the differentiated mouse brain).¹¹ Mutations associated with the maternal UBE3A gene result in Angelman syndrome.⁹

The role of ghrelin in the satiety defect found in Prader-Willi syndrome is a subject of active investigation. In 2002, Cummings et al reported significantly elevated ghrelin levels (4.5-fold higher) in individuals with Prader-Willi syndrome.¹² Haqq et al reported improvement in ghrelin levels after octreotide infusion but no significant improvement in postprandial suppression of ghrelin levels.¹³ After correction of relative hypoinsulinemia, Goldstone et al reported a residual 1.3-fold to 1.6-fold elevation in fasting ghrelin levels and a 1.2-fold to 1.5-fold elevation in postprandial ghrelin levels in adults with Prader-Willi syndrome.¹⁴

Frequency

United States

Most cases of Prader-Willi syndrome are sporadic. Burd et al reported a prevalence rate of 1 per 16,062 population.¹⁵ Butler reported a prevalence rate of 1 per 25,000 population.¹⁶

International

Prader-Willi syndrome has been reported worldwide. Reported prevalence rates for Prader-Willi syndrome range from 1 per 8000 population in rural Sweden to 1 per 16,000 population in western Japan.^17,18  Despite findings that suggest a prevalence rate of 1 per 52,000 population in the United Kingdom, Whittington et al estimate that the actual prevalence rate is higher and propose a true prevalence rate of 1 per 45,000 population.¹⁹

Mortality/Morbidity

Complications due to obesity (eg, slipped capital femoral epiphyses, sleep apnea, cor pulmonale, type 2 diabetes mellitus) and behavioral problems are major contributors to morbidity and mortality in individuals with Prader-Willi syndrome (see Complications). Lamb et al reported premature development of atherosclerosis with severe coronary artery disease in an patient aged 26 years with Prader-Willi syndrome, morbid obesity, and non–insulin-dependent diabetes mellitus.²⁰

Wharton et al described a series of 6 patients with Prader-Willi syndrome with dramatic acute gastric distention preceded by symptoms of gastroenteritis.²¹ One half of the cases rapidly progressed to massive gastric dilatation and gastric necrosis. One patient died of overwhelming sepsis and disseminated intravascular coagulation. Gastric dilatation spontaneously resolved in 2 children. Gastrectomy was performed in 2 patients; in one patient, gastrectomy was subtotal and distal, whereas in the other patient, gastrectomy was combined with partial duodenectomy and pancreatectomy. An autopsy series by Stevenson et al reported gastric rupture and necrosis as the confirmed cause of death in 3% of the patients with Prader-Willi syndrome, with another 4 suspected cases of gastric necrosis.²²

In a series of 152 patients with Prader-Willi syndrome, choking episodes were reported as the cause of death in 7.9%.²³

Another series of patients noted 8 children and 2 adults who had unexpected death, with small adrenal glands noted in 3 of 8 children, raising suspicion for underlying adrenal insufficiency.²⁴

Race

Differences in prevalence rates between racial groups have not been consistently reported. However, in a study of 10 blacks with Prader-Willi syndrome, Hudgins et al (1998) suggested that clinical features in black patients differ from those of white patients.²⁵ In black patients, growth is less affected, hand lengths are usually normal, and the facies are less typical.

Sex

Prader-Willi syndrome is caused by the loss of the paternal copy in the proximal arm of chromosome 15 in the region of 15p11-13. Differences in prevalence rates between sexes have not been reported.

Age

Prader-Willi syndrome is a genetic disorder with lifelong implications.

Clinical

History

• Infants with Prader-Willi syndrome (PWS) commonly exhibit hypotonia, poor suck (with requirement of gavage feedings), weak cry, and genital hypoplasia (eg, cryptorchidism, scrotal hypoplasia, clitoral hypoplasia).²⁶ Neonatal hypotonia is one of the hallmark features of this disorder and is a valuable clue to initiate diagnostic testing.
• Toddlers with Prader-Willi syndrome demonstrate late acquisition of major motor milestones (eg, sitting at age 12 mo, walking at age 24 mo).
• Children aged 1-6 years present with symptoms of hyperphagia with progressive development of obesity.
• Short stature is generally present during childhood; a minority of patients present later with lack of pubertal growth spurt.²⁷
• Sleep disturbances, ranging from central or obstructive sleep apnea to narcolepsy, are common.²⁸  Exacerbation of obstructive sleep apnea shortly after initiation of growth hormone therapy is a recent concern.
• Most patients with Prader-Willi syndrome have growth hormone deficiency, as determined with provocative testing.²⁷
• Pubic and axillary hair may grow prematurely in children with Prader-Willi syndrome, but other features of Prader-Willi syndrome are generally delayed or incomplete.²⁷
• Testicular descent has occurred as late as in adolescence; menarche may occur as late as age 30 years in the presence of significant weight loss.²⁷
• Patients with Prader-Willi syndrome often exhibit behavioral problems.²⁹
  • Young children exhibit temper tantrums, stubbornness, and obsessive-compulsive behaviors.
  • Behavioral issues often compromise the level of academic performance. Obsessive-compulsive behaviors and perseveration are challenging for children with Prader-Willi syndrome in the classroom setting.³⁰
  • Features of psychosis are present in 5-10% of young adults with Prader-Willi syndrome.³¹
  • Food-seeking behaviors may include eating garbage, eating frozen food, and stealing resources to obtain food. High thresholds for vomiting and pain tolerance can complicate binging on spoiled foods and delay treatment for GI disease. Death due to choking episodes has been reported.²³  After episodes of binge eating (eg, at holidays), both thin and obese individuals with Prader-Willi syndrome have developed abdominal discomfort, with acute gastric dilation observed using radiography. Some patients have developed gastric necrosis.²²
• Mild mental retardation is common.³⁰
• Obesity complications (eg, sleep apnea, cor pulmonale, diabetes mellitus, atherosclerosis), hypogonadism (osteoporosis), and behavioral issues are common problems in adults with Prader-Willi syndrome.³²

Physical

Holm et al established the following diagnostic criteria for Prader-Willi syndrome.³³ Based on these guidelines, the diagnosis of Prader-Willi syndrome is highly likely in children younger than 3 years with 5 points (3 from major criteria) or in those older than 3 years with 8 points (4 from major criteria).

• Major criteria (1 point each)
  • CNS - Infantile central hypotonia
  • GI - Infantile feeding problems and/or failure to thrive
  • Nutrition - Rapid weight gain in children aged 1-6 years
  • Craniofacial - Characteristic facial features such as narrow bifrontal diameter, almond-shaped palpebral fissures, narrow nasal bridge, and down-turned mouth
  • Endocrine - Hypogonadism
  • Developmental - Developmental delay and/or mental retardation
• Minor criteria (one half point each)
  • Neurologic - Decreased fetal movement and/or infantile lethargy
  • Pulmonary - Sleep disturbance and/or sleep apnea
  • Endocrine - Short stature for predicted height by mid adolescence
  • Dermatologic - Hypopigmentation
  • Orthopedic - Small hands and feet
  • Orthopedic - Narrow hands with straight ulnar border
  • Ophthalmologic – Esotropia and/or myopia
  • Dental - Thick viscous saliva
  • Otolaryngology - Speech articulation defects
  • Psychiatric - Skin picking (Some patients with Prader-Willi syndrome have become anemic from chronic rectal bleeding secondary to skin picking.)
• Supportive criteria (no points)
  • Neurology - High pain threshold and normal neuromuscular evaluation for hypotonia
  • Gastroenterology - Decreased vomiting 
  • Endocrinology - Ineffective thermoregulation, early adrenarche, and/or osteoporosis, adrenal insufficiency²⁷
  • Orthopedics – Scoliosis or kyphosis³⁴
  • Developmental - Jigsaw puzzle proficiency³³

Causes

• Prader-Willi syndrome is due to the loss of the paternal copy of chromosome 15q11.2-13.⁴
• Most cases of Prader-Willi syndrome are sporadic. More than 70% of patients have a deletion of the paternal copy; approximately 25% of patients with Prader-Willi syndrome have maternal uniparental disomy in chromosome 15. The remainder of patients with this disorder have a translocation or other structural alteration in chromosome 15.
• Most manifestations of Prader-Willi syndrome are attributable to hypothalamic dysfunction.

Differential Diagnoses

Other Problems to Be Considered

Angelman syndrome
Scoliosis
Hypotonia
Bardet-Biedl syndrome
Cohen syndrome
Albright hereditary osteodystrophy

Workup

Laboratory Studies

• Genetic testing^35,36
  • Genetic testing for Prader-Willi syndrome (PWS) includes chromosomal analysis and assessment for methylation patterns in the Prader-Willi syndrome region.
  • Methylation patterns can be determined with Southern blot hybridization or polymerase chain reaction (PCR) using DNA primers that can detect methylated cytosine.
  • Analysis for underlying uniparental disomy requires samples from both parents and the child with Prader-Willi syndrome.
  • Fluorescent in situ hybridization (FISH) can be used to confirm prenatal diagnosis when a deletion in the 15q region is suspected after chorionic villus sampling or amniocentesis.
  • In a patient with an imprinting center mutation, test both biological parents for the presence of asymptomatic mutations in the imprinting center; such mutations indicate a higher risk for recurrence.
• Hypogonadism^27,36
  • Most patients with Prader-Willi syndrome have hypothalamic dysfunction that manifests as short stature, central obesity, hypogonadism, and osteoporosis.
  • Fasting measurements of serum insulinlike growth factor-1 (IGF-1) and insulinlike growth factor binding protein-3 (IGFBP-3) levels are good screening measurements for underlying growth hormone deficiency.
  • Refer patients with diminished growth velocity and abnormal levels of IGF-1 and IGFBP-3 to a pediatric endocrinologist for provocative growth hormone stimulation testing.
  • Assess thyroid and adrenal status in patients when clinically warranted.
  • Hypopituitarism has been reported in some patients with Prader-Willi syndrome.
• Obesity^27,37,38,36
  • Measure glycosylated hemoglobin inpatients with Prader-Willi syndrome who are obese to assess for the development of type 2 diabetes mellitus as clinically warranted, especially if the patient is taking growth hormone supplementation.
  • Evaluate patients with Prader-Willi syndrome for biochemical evidence of pickwickian syndrome (eg, hypercarbia, polycythemia) as clinically warranted.
  • If symptoms suggest sleep apnea or narcolepsy, perform a sleep study with multiple sleep latency testing.

Imaging Studies

• Individuals with Prader-Willi syndrome are at risk for pathologic fractures secondary to underlying osteoporosis. A high pain tolerance may allow for minimal symptoms of discomfort with obvious deformity. Patients with Prader-Willi syndrome may require the following imaging studies:³⁶
  • MRI of the head (to evaluate for hypopituitarism)
  • Serial dual energy x-ray absorptiometry (DEXA) scanning (for detection and monitoring of osteoporosis)³⁹
  • Scoliosis films
    
    

    

    Severe typical scoliosis.

    
    
  • Chest radiography (if cor pulmonale is suspected)
  • Other imaging modalities as clinically dictated (eg, extremity film for limp evaluation, hip films to screen for hip dysplasia⁴⁰ )
• In patients who suddenly develop abdominal distension, abdominal pain, or a decrease in appetite, imaging including plain abdominal radiography, abdominal ultrasonography, or CT scanning and gastrointestinal series may be warranted to screen for possible conditions such as acute gastric dilation, cholelithiasis, or pancreatitis.

Procedures

• Assess the growth hormone axis and adrenal axis under the supervision of an endocrinologist if clinically warranted.²⁷

Treatment

Medical Care

• Patients with Prader-Willi syndrome (PWS) frequently require medical care for the following:³⁶
  • Initial management of hypotonia or poor feeding
  • Evaluation for hypogonadism or hypopituitarism
  • Management of obesity
  • Monitoring for scoliosis
  • Therapy for behavioral issues
• On June 20, 2000, the US Food and Drug Administration (FDA) approved the use of growth hormone in children with genetically confirmed Prader-Willi syndrome and evidence of growth failure.^41,42

Surgical Care

• Patients with Prader-Willi syndrome may require surgical care for treatment of complications of obesity, treatment of cryptorchidism, and scoliosis intervention. They may require urgent surgical attention for abdominal issues. Because of the high pain tolerance and decreased ability to vomit, they may present late with symptoms of cholecystitis, appendicitis, or acute gastric dilation with risk for progression to necrosis.^21,22
• Tonsillectomy, adenoidectomy, or tracheostomy placement may be required in patients with obstructive sleep apnea.
• Biliopancreatic diversion and gastric bypass surgery have been ineffective for long-term weight reduction.^43,44 Significant disruption in the enterohepatic circulation of bile acids may result in deficiencies of fat-soluble vitamins and steatorrhea with anal pruritus due to bile acids. Anal pruritus may exacerbate rectal-picking compulsions. Deficiencies of fat-soluble vitamins may exacerbate the following:
  • Osteoporosis (vitamin D)
  • Hypochromic anemia (vitamin E)
  • Hyporeflexia (vitamin E)
  • Spinocerebellar ataxia (vitamin E)
  • Coagulopathy (vitamin K)
  • Night blindness (vitamin A)
  • Enhanced susceptibility to infections (vitamin A)

Consultations

Patients with Prader-Willi syndrome may require the support of the following specialists:⁴⁰

• Geneticist for initial diagnosis and counseling
• Developmental pediatrician for stimulation programs
• Endocrinologist for management of hypogonadism
• Nutritionist for dietary counseling
• Ophthalmologist for management of strabismus
• Pulmonologist for management of sleep apnea
• Psychiatrist, psychologist, or both for management of behavioral issues
• Gastroenterologist for GI issues

Diet

Patients with Prader-Willi syndrome have hyperphagia (onset in children aged 1-6 y) and diminished basal metabolic rate. Various treatment modalities for weight control, ranging from behavioral modification to anorexic agents, have been largely unsuccessful in curbing hyperphagia. However, these modalities may yield some success when used at group home settings.^40,44

• Significant dietary restrictions are not implemented during early childhood to ensure optimal myelination.
• Institution of a balanced hypocaloric diet (1000 calories with supplementation of vitamins and calcium) is generally implemented at early school age with careful monitoring by a dietitian.
• As children with Prader-Willi syndrome become ambulatory, limitation of access to foods is essential for modulation of weight. Placement of locks on cupboards and refrigerators, use of smaller dishes, and restriction of access to food in the school environment help deter excessive weight gain.
• In patients with morbid obesity, a protein-sparing modified fast with careful medical and nutritional supervision over several weeks may facilitate short-term weight loss.⁴⁵

Activity

• Patients with Prader-Willi syndrome have hypotonia and require supplemental occupational and physical therapy to promote acquisition of gross and fine motor skills and to strengthen spinal musculature in order to minimize scoliosis.³⁴
• Encouragement of physical activity at home, at school (eg, increased physical education periods), and in the community (eg, Special Olympics) is essential for modulation of weight. 
• Care providers should be instructed in the Heimlich maneuver.²³

Medication

Currently, no medications have been found to effectively modify hyperphagia. Growth hormone therapy in patients with growth hormone deficiency improves lean body mass, corrects osteopenia, does not appear to enhance the development of scoliosis, and anecdotally modulates behavior in some patients.^27,41,42 Supplementation of sex steroids does improve secondary sex characteristics but may aggravate behavioral disorders.²⁷

Growth hormone agents

These agents improve symptoms of growth hormone deficiency.

Human growth hormone (Saizen, Genotropin, Humatrope, Nutropin, Serostim)

Stimulates growth of linear bone, skeletal muscle, and organs. Stimulates erythropoietin, increasing RBC mass.

Dosing

Adult

Not established

Pediatric

0.15-0.3 mg/kg/wk SC initially; divide into daily or 6 times/wk subcutaneous injections; adjust dose to effect

Interactions

Glucocorticoids may decrease growth-promoting effects

Contraindications

Documented hypersensitivity; closed epiphyses; actively growing intracranial tumor; any underlying intracranial lesion

Precautions

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Caution in diabetes; reconstitute with sterile water for injection if administering to newborns

Follow-up

Further Inpatient Care

• Patients with Prader-Willi syndrome (PWS) may require inpatient evaluation and treatment for hypotonia and poor feeding during infancy.
• Individuals with Prader-Willi syndrome and other medical issues, including scoliosis and complications of obesity or pickwickian syndrome, may require inpatient therapy.
• Patients with severe behavioral problems may merit admission to a facility staffed with individuals with long-term experience with Prader-Willi syndrome.

Further Outpatient Care

• Further outpatient care is targeted toward management of hypogonadism, obesity, and behavioral issues.

Transfer

• Patients with Prader-Willi syndrome and significant behavioral issues recalcitrant to traditional therapies may benefit from transfer to a center, such as the Children's Institute in Pittsburgh, staffed with individuals with experience in treatment of people with Prader-Willi syndrome.

Deterrence/Prevention

• Patients with Prader-Willi syndrome have hyperphagia and require restricted access to foods to minimize weight gain. Binge-eating episodes may predispose patients to development of food poisoning and acute gastric dilation. Caregivers of patients with Prader-Willi syndrome should be instructed in the Heimlich maneuver.²³
• Evaluate males with Prader-Willi syndrome and cryptorchidism for gonadotropin-releasing hormone (GnRH) and orchiopexy.²⁷
• Routinely monitor for symptoms of sleep apnea. Obtain a sleep study within the few months after initiation of growth hormone therapy at the first sign of symptoms.⁴¹
• Routinely screen children for scoliosis.^34,40
• Regularly screen patients with obesity for evidence of type 2 diabetes mellitus.²⁷
• Screen for thyroid and adrenal function when indicated.⁴⁰

Complications

• Patients with Prader-Willi syndrome can develop complications from the following:
  • Hypogonadism (osteoporosis/pathologic fractures)
  • Obesity due to hyperphagia and hypometabolism (secondary to hypopituitarism): This predisposes patients to premature death from cardiorespiratory failure.
  • Slipped capital femoral epiphyses/hip dysplasia
  • Sleep apnea: Patients with Prader-Willi syndrome have a primary disturbance in central control of the respiratory drive with diminished responsiveness to hypercapnia during quiet sleep.
  • Cor pulmonale
  • Type 2 diabetes mellitus
  • Neoplasias (eg, Wilms tumors,⁴⁶ testicular neoplasias,⁴⁷  multiple endocrine neoplasia [MEN1],⁴⁸ neoplasias, hematologic neoplasias [leukemia]⁴⁹ ): Various neoplasias have been rarely reported in patients with Prader-Willi syndrome.
  • Binge-eating episodes: These episodes may predispose patients to choking episodes (which require the Heimlich maneuver), acute gastric dilation with risk of gastric necrosis, and food poisoning from consumption of contaminated food.^21,23

Prognosis

• Patients with Prader-Willi syndrome frequently reach adulthood and are able to function in a group home setting, performing vocational work or attending community college classes.
• Diminished sensitivity to pain and diminished capacity to vomit may delay the diagnosis of underlying disease (eg, appendicitis).
• Complications from hypogonadism (eg, osteoporosis/pathologic fracture), behavioral issues (eg, temper tantrums, stubbornness, psychoses), and morbid obesity (eg, type 2 diabetes mellitus, cor pulmonale) may shorten life expectancy and may affect the quality of life.
• Patients with Prader-Willi syndrome can be mainstreamed into the classroom environment. They require additional speech therapy to enhance verbal skills and should have additional physical activity periods in place of rest periods. These individuals require a structured environment and may need a smaller classroom size for individual attention.
• Older children with Prader-Willi syndrome may enter vocational programs (with avoidance of food preparation). Some adults have attended community colleges.

Miscellaneous

Medicolegal Pitfalls

• Potential medicolegal pitfalls involving care of patients with Prader-Willi syndrome (PWS) include failure to appropriately manage cryptorchidism, failure to appropriately manage obesity and its associated complications, and failure to appropriately investigate reports of pain or emesis.
• Patients with Prader-Willi syndrome have a very high threshold for pain and emesis; they can develop ipecac toxicity and have been known to have minimal reports of abdominal discomfort in the presence of significant gastrointestinal pathology such as pancreatitis, acute gastric dilation with necrosis, appendicitis, and cholecystitis.

Special Concerns

• The following Web sites provide excellent resources regarding Prader-Willi syndrome:
  • Prader-Willi Syndrome Association
  • Prader-Willi Syndrome Arizona Association
  • Ontario Prader-Willi Syndrome Association
  • Foundation for Prader-Willi Research (FPWR)
  • International Prader-Willi Syndrome Organization

Multimedia

Media file 1: Severe typical scoliosis.

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Keywords

PWS, Prader-Labhart-Willi syndrome, Prader-Willi syndrome, chromosomal microdeletion, disomy disorder, diminished fetal activity, obesity, hypotonia, mental retardation, short stature, hypogonadotropic hypogonadism, strabismus, polysarcia, Angelman syndrome, ghrelin, hypoinsulinemia, slipped capital femoral epiphyses, sleep apnea, cor pulmonale, diabetes mellitus type II, obsessive-compulsive behavior, developmental delay, sleep disturbance, hypopigmentation, hypothalamic dysfunction, treatment, diagnosis

Contributor Information and Disclosures

Author

Ann Scheimann, MD, MBA, Associate Professor, Department of Pediatrics, Section of Nutrition and Gastroenterology, Baylor College of Medicine and Johns Hopkins Medical Institution
Ann Scheimann, MD, MBA is a member of the following medical societies: North American Society for Pediatric Gastroenterology and Nutrition
Disclosure: Nothing to disclose.

Medical Editor

Michael Fasullo, PhD, Senior Scientist, Ordway Research Institute; Associate Professor, State University of New York at Albany; Adjunct Associate Professor, Center for Immunology and Microbial Disease, Albany Medical College
Michael Fasullo, PhD is a member of the following medical societies: Radiation Research Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Robert Anthony Saul, MD, Clinical Professor, Department of Pediatrics, University of South Carolina; Senior Clinical Geneticist, Greenwood Genetic Center
Robert Anthony Saul, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics, and American College of Physician Executives
Disclosure: Nothing to disclose.

CME Editor

Paul D Petry, DO, FACOP, FAAP, Consulting Staff, Freeman Pediatric Care, Freeman Health System
Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD, Professor, Department of Pediatrics, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics, University of Nebraska Medical Center
Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association
Disclosure: Nothing to disclose.

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